Latinos suffer a greater disability burden from depression than whites due to low rates of quality depression care. Depression is common among Latinos in primary care settings and is also often chronic, recurring, and comorbid with chronic medical illness. Improving outcomes for both depression and chronic medical illness requires patients to become educated, active partners in managing their illnesses. Latinos desire education regarding general and mental health; have stigma-related concerns regarding mental health care; and prefer psychotherapy to medication. However, safety net primary care providers and clinics often prioritize improving medical outcomes and lack the resources for depression care, especially psychotherapy. There is an important public health need to develop a culturally relevant, low cost intervention that includes educational and psychotherapeutic elements, targets medical illness and depression, and destigmatizes depression care. In response to patient, provider, and clinic preferences and resources for depression care, in prior work, we developed but have not yet tested an innovative, theoretically-based group intervention, drawing upon two evidence-based interventions that improve self-efficacy: group cognitive behavioral therapy (CBT) for depression and group self-management for chronic medical illness. Professionally-led group CBT is effective for depression among ethnic minorities in primary care but is difficult to sustain. Among patients with chronic medical illness, lay-led group self-management programs educate and empower patients to engage in healthful behaviors and participate in their care. The groups improve self-efficacy, health-related behaviors, and outcomes; have been adapted for diverse conditions; and have been widely disseminated and sustained. However, standard self-management groups do not improve depression. We thus enhanced the Spanish- language Tomando Control de su Salud chronic disease self-management program by adding depression- related educational and skill-building content from group CBT. We propose to pilot test and refine Cuerpo Sano, Mente Sana, our newly enhanced Spanish-language self- management program for depression and chronic medical illness. Following a framework for successful implementation of interventions, we 1) evaluate intervention context and refine our intervention and implementation strategy; 2) conduct a randomized trial with 30 low-income Spanish-speaking patients with depressive disorder and chronic medical illness; 3) review pilot findings of feasibility, implementation, and potential sustainability with a multistakeholder panel and revise materials and procedures; 4) conduct a subsequent trial with 30 additional patients; and 5) review additional findings (now including 3- and 6-month intervention effects on self-efficacy, self-care behaviors, and depression and health outcomes) with clinic stakeholders and finalize the intervention and implementation strategy. This study lays the groundwork for future comparative effectiveness studies of strategies to improve care for Latinos in safety net primary care.